Family members and well-wishers gathered at the CFB Halifax dockyard to say goodbye.
For Melissa McQuaid, it's her fourth time seeing off her husband for a deployment. She was at the dockyard with daughter Dakota and son Damian.
"It's always on the back of your mind what's going to happen. So, as long as they're safe, that's all we care about," she said.
There are 250 military personnel of all ranks aboard HMCS Fredericton. The frigate also carries a Sea King helicopter.
Operation Reassurance is part of a larger NATO response to what's happening in Ukraine. Fredericton's role is to provide support to its allies, from surveillance to "regional defence and diplomatic engagement," according to a government news release.
HMCS Fredericton will replace HMCS Toronto, which left Halifax in July and began its NATO mission in August.
"Toronto needs you. They've been there a long time and they want to come home and have their Christmas. To them, the best gift will be to see you arriving in Spain and doing a turnover with them," said Rear Admiral John Newton during Tuesday's news conference.
In September, HMCS Toronto was circled by one Russian surveillance plane and two fighter jets in the Black Sea, according to the defence minister's office.
Defence Minister Rob Nicholson said Russia's military acted in an "unnecessarily provocative" manner.
On Christmas Day, a fire broke out aboard HMCS Toronto but the Department of National Defence said it was put out quickly and no one was hurt.Suggest a correction